A study of monophasic supramolecular formulation of Sulpiride with P-glycoprotein efflux inhibitor to enhance solubility and intestinal permeability with molecular modeling insights

Abstract

Abstract The aim of the study was to design and develop a supramolecular formulation of sulpiride (SUL) to enhance its solubility, dissolution, and permeability. This was accomplished by co-amorphizing SUL with Naringin (NARI) to improve its physicochemical properties. In addition, NARI was incorporated as a co-former to enhance the drug's intestinal permeability by targeting P-glycoprotein (P-gp) inhibition. To confirm the intermolecular interaction and formation of the co-amorphous system, extensive characterization was performed. This included quantum mechanics-based molecular dynamics simulation studies investigating intermolecular interactions and phase transformation. The findings of the miscibility study, Radial Distribution Function (RDF) analysis, and quantitative simulations of hydrogen/π-π bond interactions helped in comprehending the co-amorphization aspects of SUL-NARI systems. Molecular docking studies were conducted to predict the in-silico biological activity. The solubility, dissolution, and ex-vivo permeability studies were performed to determine the extent of improvement in solubility, dissolution and flux, demonstrating 31.88-fold, 9.13-fold, and 1.91-fold increments, respectively. In conclusion, this study demonstrates the benefits of synthesizing a drug-nutraceutical supramolecular formulation to enhance the solubility and permeability of poorly soluble and permeable drug.